The elemental isotope definition used to calculate the theoretical masses and isotope distribution of (bio)molecules is
considered to be a fixed, universal standard in mass-spectrometrybased proteomics. However, this is an incorrect assumption. In view of the ongoing advances in mass spectrometry technology, and in particular the ever-increasing mass precision, the elemental isotope definition and its variations should be taken into account. We illustrate the effect of the elemental isotope uncertainty on the theoretical and experimental masses with theoretical calculations and examples.